Many molecules enter the cell interior within clathrin-coated vesicles, in process termed endocytosis. This process is critical to the way we move and think. At the tip of each axon, synaptic vesicles (packages of neurotransmitter) release their contents when the nerve is stimulated by fusing with the cell surface. Almost instantly, the membrane of the synaptic vesicle is then retrieved within clathrin-coated vesicles. Endocytosis is thus tightly coupled to exocytosis, the stimulated release of neurotransmitter. Failure to recover synaptic-vesicle membrane results in both morphological disruption of the nerve terminal and defective neurotransmission. We study the mechanisms and molecules involved in clathrin-coat assembly. To understand how these complex structures assemble within only a minute or two, we use biochemical, cell biological and structural approaches to unravel the protein-protein interactions that orchestrate the formation of this elaborate protein-sorting machine.
- Traub, L.M. and Lukacs, G.L. Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs. J. Cell Sci. 120: 543-553, 2007.
- Brett, T.J. and L.M. Traub. Molecular structures of coat and coat-associated proteins: function follows form. Curr. Opin. Cell Biol. 18: 395-406, 2006.
- Edeling, M.A., S.K. Mishra, P.A. Keyel, A.L. Steinhauser, B.M. Collins, R. Roth, J.E. Heuser, D.J. Owen, and L.M. Traub. Molecular switches Involving the AP-2 β2 appendage regulate endocytic cargo selection and clathrin coat assembly. Dev. Cell 10: 329-342, 2006.
- Hawryluk, M.J., P.A. Keyel, S.K. Mishra, S.C. Watkins, J.E. Heuser, and L.M. Traub. Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein. Traffic 7: 262-281, 2006.
- Keyel, P.A., S.K. Mishra, R. Roth, J.E. Heuser, S.C. Watkins, and L.M. Traub. A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Mol. Biol. Cell 17: 4300-4317, 2006.
- Mishra, S.K., P.A. Keyel, M.A. Edeling, A.L. Dupin, D.J. Owen and L.M. Traub. Functional dissection of an AP-2 β2 appendage-binding sequence within the autosomal recessive hypercholesterolemia (ARH) protein. J. Biol. Chem. 280: 19270-19280, 2005
- Miele, A.E., P.J. Watson, P.R. Evans, L.M. Traub and D.J. Owen. Two distinct interaction motifs in amphiphysin bind two independent sites on the clathrin terminal domain β-propeller. Nat. Struc. & Mol. Biol. 11: 242-248, 2004.
- Bonifacino, J.S., and L.M. Traub. Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu. Rev. Biochem. 72: 395-447, 2003.
- Traub, L.M. Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection. J. Cell Biol. 163: 203-208, 2003
- Mishra, S.K., P. A. Keyel, M. J. Hawryluk, N.R. Agostinelli, S. C. Watkins and L.M. Traub. Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor. EMBO J. 21: 4915-4926, 2002.
- Mishra, S.K., S.C. Watkins and L.M. Traub. The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery. Proc. Natl. Acad. Sci. U S A. 99:16099-16104, 2002.
University of Pittsburgh
Department of Cell Biology